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PloS one2021; 16(11); e0257819; doi: 10.1371/journal.pone.0257819

First clinical expression of equine insect bite hypersensitivity is associated with co-sensitization to multiple Culicoides allergens.

Abstract: Insect bite hypersensitivity (IBH) is an IgE-mediated allergic dermatitis in horses incited by salivary allergens from Culicoides spp. IBH does not occur in Iceland, as the causative agents are absent, however a high prevalence is seen in horses exported to Culicoides-rich environments. To study the natural course of sensitization to Culicoides allergens and identify the primary sensitizing allergen(s) in horses exported from Iceland utilizing a comprehensive panel of Culicoides recombinant (r-) allergens. IgE microarray profiling to 27 Culicoides r-allergens was conducted on 110 serological samples from horses imported to Switzerland from Iceland that subsequently developed IBH or remained healthy. Furthermore, a longitudinal study of 31 IBH horses determined IgE profiles the summer preceding first clinical signs of IBH (TIBH-1), the summer of first clinical signs (TIBH) and the following summer (TIBH+1). In a group of Icelandic horses residing in Sweden, effects of origin (born in Iceland or Sweden) and duration of IBH (<4 years, 4-7 years, >7 years) on Culicoides-specific IgE was evaluated. Sero-positivity rates and IgE levels were compared. At TIBH, horses were sensitized to a median of 11 r-allergens (range = 0-21), of which nine were major allergens. This was significantly higher than TIBH-1 (3, 0-16), as well as the healthy (1, 0-14) group. There was no significant increase between TIBH and TIBH+1(12, 0-23). IBH-affected horses exported from Iceland had a significantly higher degree of sensitization than those born in Europe, while duration of IBH did not significantly affect degree of sensitization. Significant sensitization is only detected in serum the year of first clinical signs of IBH. Horses become sensitized simultaneously to multiple Culicoides r-allergens, indicating that IgE-reactivity is due to co-sensitization rather than cross-reactivity between Culicoides allergens. Nine major first sensitizing r-allergens have been identified, which could be used for preventive allergen immunotherapy.
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Publication Date: 2021-11-15 PubMed ID: 34780496PubMed Central: PMC8592417DOI: 10.1371/journal.pone.0257819Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research studied the sensitization to Culicoides allergens in horses that cause Insect Bite Hypersensitivity (IBH), an allergic reaction. The study found that horses show significant sensitization in the year they first display clinical signs of IBH, typically reacting to multiple allergens simultaneously. This understanding could be used to develop preventive allergen immunotherapy treatments for horses.

Understanding the Development of Allergic Sensitization in Horses

  • The study focused on understanding the development and patterns of allergic sensitization to Culicoides allergens in horses, specifically those related to Insect Bite Hypersensitivity (IBH). It intended to identify the primary allergens causing this reaction.
  • IgE microarray profiling was used to study 110 serological samples from horses imported from Iceland (where IBH does not occur due to the absence of causative agents) to Switzerland, which is a Culicoides-rich environment.
  • The study also included a longitudinal analysis of 31 horses showing signs of IBH over three summers: before the first clinical signs (TIBH-1), the summer of the first clinical signs (TIBH), and the following summer (TIBH+1).

Results and Findings

  • The study found that horses were sensitized to a median of 11 recombinant (r-) allergens during the summer of their first clinical signs of IBH. This number was significantly higher than the summer before their first signs and the number of allergens sensitized to by healthy horses.
  • The research also found that there was no significant increase in the number of allergens the horses were sensitized to between the TIBH and TIBH+1 phases.
  • The results revealed that horses with IBH that had been exported from Iceland showed a higher degree of sensitization than those born in Europe.

Implications and Practical Applications

  • The findings suggest that significant sensitization occurs only in the year horses show their first clinical signs of IBH.
  • It was discovered that horses typically become sensitized to multiple Culicoides r-allergens at the same time. This suggests that the IgE-reactivity observed in horses with IBH is more a result of co-sensitization to multiple allergens than cross-reactivity between different Culicoides allergens.
  • The study also identified nine major allergens that horses tend to become sensitized to first. These findings could be instrumental in developing preventive allergen immunotherapy for horses at risk of developing IBH.

Cite This Article

APA
Birras J, White SJ, Jonsdottir S, Novotny EN, Ziegler A, Wilson AD, Frey R, Torsteinsdottir S, Alcocer M, Marti E. (2021). First clinical expression of equine insect bite hypersensitivity is associated with co-sensitization to multiple Culicoides allergens. PLoS One, 16(11), e0257819. https://doi.org/10.1371/journal.pone.0257819

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 16
Issue: 11
Pages: e0257819
PII: e0257819

Researcher Affiliations

Birras, Jasmin
  • Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
White, Samuel J
  • School of Animal, Rural and Environmental Sciences, Nottingham Trent University, Brackenhurst Campus, Southwell, United Kingdom.
  • School of Biosciences, University of Nottingham, Loughborough, United Kingdom.
Jonsdottir, Sigridur
  • Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Institute for Experimental Pathology, Biomedical Center, University of Iceland, Keldur, Reykjavik, Iceland.
Novotny, Ella N
  • Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Ziegler, Anja
  • Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Wilson, A Douglas
  • Division of Veterinary Pathology, Infection and Immunity, University of Bristol, Langford, United Kingdom.
Frey, Rebecka
  • AniCura Norsholms Djursjukhus, Norsholm, Sweden.
Torsteinsdottir, Sigurbjörg
  • Institute for Experimental Pathology, Biomedical Center, University of Iceland, Keldur, Reykjavik, Iceland.
Alcocer, Marcos
  • School of Biosciences, University of Nottingham, Loughborough, United Kingdom.
Marti, Eliane
  • Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Bern, Switzerland.

MeSH Terms

  • Allergens / immunology
  • Animals
  • Ceratopogonidae / immunology
  • Cross Reactions
  • Dermatitis, Atopic / blood
  • Dermatitis, Atopic / immunology
  • Horse Diseases / blood
  • Horse Diseases / immunology
  • Horses / immunology
  • Iceland
  • Immunoglobulin E / blood
  • Insect Bites and Stings / blood
  • Insect Bites and Stings / immunology
  • Longitudinal Studies
  • Protein Array Analysis / methods
  • Seasons
  • Sweden
  • Switzerland

Conflict of Interest Statement

The authors have declared that no competing interests exist.

References

This article includes 32 references
  1. Schaffartzik A, Hamza E, Janda J, Crameri R, Marti E, Rhyner C. Equine insect bite hypersensitivity: what do we know?. Vet Immunol Immunopathol 2012 Jun 30;147(3-4):113-26.
    doi: 10.1016/j.vetimm.2012.03.017pubmed: 22575371google scholar: lookup
  2. Jonsdottir S, Cvitas I, Svansson V, Fettelschloss-Gabriel A, Torsteinsdottir S, Marti E. New Strategies for Prevention and Treatment of Insect Bite Hypersensitivity in Horses. Current Dermatology Reports 2019;8(4):303–12.
  3. Björnsdóttir S, Sigvaldadóttir J, Broström H, Langvad B, Sigurdsson A. Summer eczema in exported Icelandic horses: influence of environmental and genetic factors.. Acta Vet Scand 2006 May 26;48(1):3.
    doi: 10.1186/1751-0147-48-3pmc: PMC1513129pubmed: 16987399google scholar: lookup
  4. Sommer-Locher B, Endriss V, Fromm E. Various Circumstances Regarding Initial Allergen Exposure and Their Influence on Development of Insect Bite Hypersensitivity in Horses. Journal of Equine Veterinary Science 2012;32(3):158–63.
  5. Eckl-Dorna J, Villazala-Merino S, Linhart B, Karaulov AV, Zhernov Y, Khaitov M, Niederberger-Leppin V, Valenta R. Allergen-Specific Antibodies Regulate Secondary Allergen-Specific Immune Responses.. Front Immunol 2018;9:3131.
    doi: 10.3389/fimmu.2018.03131pmc: PMC6344431pubmed: 30705676google scholar: lookup
  6. Barbet JL, Bevier D, Greiner EC. Specific immunotherapy in the treatment of Culicoides hypersensitive horses: a double-blind study.. Equine Vet J 1990 Jul;22(4):232-5.
    doi: 10.1111/j.2042-3306.1990.tb04258.xpubmed: 2209518google scholar: lookup
  7. Ginel PJ, Hernández E, Lucena R, Blanco B, Novales M, Mozos E. Allergen-specific immunotherapy in horses with insect bite hypersensitivity: a double-blind, randomized, placebo-controlled study.. Vet Dermatol 2014 Feb;25(1):29-e10.
    doi: 10.1111/vde.12092pubmed: 24267396google scholar: lookup
  8. van der Meide NM, Roders N, Sloet van Oldruitenborgh-Oosterbaan MM, Schaap PJ, van Oers MM, Leibold W, Savelkoul HF, Tijhaar E. Cloning and expression of candidate allergens from Culicoides obsoletus for diagnosis of insect bite hypersensitivity in horses.. Vet Immunol Immunopathol 2013 Jun 15;153(3-4):227-39.
    doi: 10.1016/j.vetimm.2013.03.005pubmed: 23561552google scholar: lookup
  9. Peeters LM, Janssens S, Goddeeris BM, De Keyser K, Wilson AD, Kaufmann C, Schaffartzik A, Marti E, Buys N. Evaluation of an IgE ELISA with Culicoides spp. extracts and recombinant salivary antigens for diagnosis of insect bite hypersensitivity in Warmblood horses.. Vet J 2013 Oct;198(1):141-7.
    doi: 10.1016/j.tvjl.2013.06.010pubmed: 23891138google scholar: lookup
  10. Novotny EN, White SJ, Wilson AD, Stefánsdóttir SB, Tijhaar E, Jonsdóttir S, Frey R, Reiche D, Rose H, Rhyner C, Schüpbach-Regula G, Torsteinsdóttir S, Alcocer M, Marti E. Component-resolved microarray analysis of IgE sensitization profiles to Culicoides recombinant allergens in horses with insect bite hypersensitivity.. Allergy 2021 Apr;76(4):1147-1157.
    doi: 10.1111/all.14556pmc: PMC8246938pubmed: 32780483google scholar: lookup
  11. Schaffartzik A, Marti E, Crameri R, Rhyner C. Cloning, production and characterization of antigen 5 like proteins from Simulium vittatum and Culicoides nubeculosus, the first cross-reactive allergen associated with equine insect bite hypersensitivity.. Vet Immunol Immunopathol 2010 Sep 15;137(1-2):76-83.
    doi: 10.1016/j.vetimm.2010.04.012pubmed: 20537727google scholar: lookup
  12. Schaffartzik A, Marti E, Torsteinsdottir S, Mellor PS, Crameri R, Rhyner C. Selective cloning, characterization, and production of the Culicoides nubeculosus salivary gland allergen repertoire associated with equine insect bite hypersensitivity.. Vet Immunol Immunopathol 2011 Feb 15;139(2-4):200-9.
    doi: 10.1016/j.vetimm.2010.10.015pubmed: 21071100google scholar: lookup
  13. Langner KF, Jarvis DL, Nimtz M, Heselhaus JE, McHolland LE, Leibold W, Drolet BS. Identification, expression and characterisation of a major salivary allergen (Cul s 1) of the biting midge Culicoides sonorensis relevant for summer eczema in horses.. Int J Parasitol 2009 Jan;39(2):243-50.
    doi: 10.1016/j.ijpara.2008.06.008pmc: PMC2744044pubmed: 18708061google scholar: lookup
  14. van der Meide NM, Meulenbroeks C, van Altena C, Schurink A, Ducro BJ, Wagner B, Leibold W, Rohwer J, Jacobs F, van Oldruitenborgh-Oosterbaan MM, Savelkoul HF, Tijhaar E. Culicoides obsoletus extract relevant for diagnostics of insect bite hypersensitivity in horses.. Vet Immunol Immunopathol 2012 Oct 15;149(3-4):245-54.
    doi: 10.1016/j.vetimm.2012.07.007pubmed: 22906994google scholar: lookup
  15. Akinfenwa O, Rodríguez-Domínguez A, Vrtala S, Valenta R, Campana R. Novel vaccines for allergen-specific immunotherapy.. Curr Opin Allergy Clin Immunol 2021 Feb 1;21(1):86-99.
    doi: 10.1097/ACI.0000000000000706pmc: PMC7810419pubmed: 33369572google scholar: lookup
  16. Tulaeva I, Kratzer B, Campana R, Curin M, van Hage M, Karsonova A, Riabova K, Karaulov A, Khaitov M, Pickl WF, Valenta R. Preventive Allergen-Specific Vaccination Against Allergy: Mission Possible?. Front Immunol 2020;11:1368.
    doi: 10.3389/fimmu.2020.01368pmc: PMC7358538pubmed: 32733455google scholar: lookup
  17. Campana R, Marth K, Zieglmayer P, Weber M, Lupinek C, Zhernov Y, Elisyutina O, Khaitov M, Rigler E, Westritschnig K, Berger U, Wolkersdorfer M, Horak F Jr, Horak F, Valenta R. Vaccination of nonallergic individuals with recombinant hypoallergenic fragments of birch pollen allergen Bet v 1: Safety, effects, and mechanisms.. J Allergy Clin Immunol 2019 Mar;143(3):1258-1261.
    doi: 10.1016/j.jaci.2018.11.011pmc: PMC6411133pubmed: 30471304google scholar: lookup
  18. Torsteinsdottir S, Scheidegger S, Baselgia S, Jonsdottir S, Svansson V, Björnsdottir S, Marti E. A prospective study on insect bite hypersensitivity in horses exported from Iceland into Switzerland.. Acta Vet Scand 2018 Nov 3;60(1):69.
    doi: 10.1186/s13028-018-0425-1pmc: PMC6215642pubmed: 30390694google scholar: lookup
  19. Ziegler A, Hamza E, Jonsdottir S, Rhyner C, Wagner B, Schüpbach G, Svansson V, Torsteinsdottir S, Marti E. Longitudinal analysis of allergen-specific IgE and IgG subclasses as potential predictors of insect bite hypersensitivity following first exposure to Culicoides in Icelandic horses.. Vet Dermatol 2018 Feb;29(1):51-e22.
    doi: 10.1111/vde.12493pubmed: 28980353google scholar: lookup
  20. Frey R, Bergvall K, Egenvall A. Allergen-specific IgE in Icelandic horses with insect bite hypersensitivity and healthy controls, assessed by FcepsilonR1alpha-based serology.. Vet Immunol Immunopathol 2008 Nov 15;126(1-2):102-9.
    doi: 10.1016/j.vetimm.2008.06.010pubmed: 18676025google scholar: lookup
  21. Heimann M, Janda J, Sigurdardottir OG, Svansson V, Klukowska J, von Tscharner C, Doherr M, Broström H, Andersson LS, Einarsson S, Marti E, Torsteinsdottir S. Skin-infiltrating T cells and cytokine expression in Icelandic horses affected with insect bite hypersensitivity: a possible role for regulatory T cells.. Vet Immunol Immunopathol 2011 Mar 15;140(1-2):63-74.
    doi: 10.1016/j.vetimm.2010.11.016pubmed: 21168921google scholar: lookup
  22. White SJ, Moore-Colyer M, Marti E, Hannant D, Gerber V, Coüetil L, Richard EA, Alcocer M. Antigen array for serological diagnosis and novel allergen identification in severe equine asthma.. Sci Rep 2019 Oct 23;9(1):15170.
    doi: 10.1038/s41598-019-51820-7pmc: PMC6811683pubmed: 31645629google scholar: lookup
  23. White S, Moore-Colyer M, Marti E, Coüetil L, Hannant D, Richard EA, Alcocer M. Development of a comprehensive protein microarray for immunoglobulin E profiling in horses with severe asthma.. J Vet Intern Med 2019 Sep;33(5):2327-2335.
    doi: 10.1111/jvim.15564pmc: PMC6766494pubmed: 31429513google scholar: lookup
  24. Wilson AD, Harwood L, Torsteinsdottir S, Marti E. Production of monoclonal antibodies specific for native equine IgE and their application to monitor total serum IgE responses in Icelandic and non-Icelandic horses with insect bite dermal hypersensitivity.. Vet Immunol Immunopathol 2006 Aug 15;112(3-4):156-70.
    doi: 10.1016/j.vetimm.2006.02.003pubmed: 16574245google scholar: lookup
  25. Wilson AD, Heesom KJ, Mawby WJ, Mellor PS, Russell CL. Identification of abundant proteins and potential allergens in Culicoides nubeculosus salivary glands.. Vet Immunol Immunopathol 2008 Mar 15;122(1-2):94-103.
    doi: 10.1016/j.vetimm.2007.10.011pubmed: 18068808google scholar: lookup
  26. Hamza E, Torsteinsdottir S, Eydal M, Frey CF, Mirkovitch J, Brcic M, Wagner B, Wilson AD, Jungi TW, Marti E. Increased IL-4 and decreased regulatory cytokine production following relocation of Icelandic horses from a high to low endoparasite environment.. Vet Immunol Immunopathol 2010 Jan 15;133(1):40-50.
    doi: 10.1016/j.vetimm.2009.07.002pubmed: 19640590google scholar: lookup
  27. Shamji MH, Durham SR. Mechanisms of allergen immunotherapy for inhaled allergens and predictive biomarkers.. J Allergy Clin Immunol 2017 Dec;140(6):1485-1498.
    doi: 10.1016/j.jaci.2017.10.010pubmed: 29221580google scholar: lookup
  28. Meulenbroeks C, van der Lugt JJ, van der Meide NM, Willemse T, Rutten VP, Zaiss DM. Allergen-Specific Cytokine Polarization Protects Shetland Ponies against Culicoides obsoletus-Induced Insect Bite Hypersensitivity.. PLoS One 2015;10(4):e0122090.
    doi: 10.1371/journal.pone.0122090pmc: PMC4406554pubmed: 25901733google scholar: lookup
  29. Hamza E, Akdis CA, Wagner B, Steinbach F, Marti E. In vitro induction of functional allergen-specific CD4+ CD25high Treg cells in horses affected with insect bite hypersensitivity.. Clin Exp Allergy 2013 Aug;43(8):889-901.
    pubmed: 23889243doi: 10.1111/cea.12131google scholar: lookup
  30. Hamza E, Wagner B, Jungi TW, Mirkovitch J, Marti E. Reduced incidence of insect-bite hypersensitivity in Icelandic horses is associated with a down-regulation of interleukin-4 by interleukin-10 and transforming growth factor-beta1.. Vet Immunol Immunopathol 2008 Mar 15;122(1-2):65-75.
    doi: 10.1016/j.vetimm.2007.10.018pubmed: 18082270google scholar: lookup
  31. Lewis MJ, Wagner B, Woof JM. The different effector function capabilities of the seven equine IgG subclasses have implications for vaccine strategies.. Mol Immunol 2008 Feb;45(3):818-27.
    doi: 10.1016/j.molimm.2007.06.158pmc: PMC2075531pubmed: 17669496google scholar: lookup
  32. Raza F, Ivanek R, Freer H, Reiche D, Rose H, Torsteinsdóttir S, Svansson V, Björnsdóttir S, Wagner B. Cul o 2 specific IgG3/5 antibodies predicted Culicoides hypersensitivity in a group imported Icelandic horses.. BMC Vet Res 2020 Aug 10;16(1):283.
    doi: 10.1186/s12917-020-02499-wpmc: PMC7418374pubmed: 32778104google scholar: lookup

Citations

This article has been cited 4 times.
  1. Cox A, Stewart AJ. Insect Bite Hypersensitivity in Horses: Causes, Diagnosis, Scoring and New Therapies. Animals (Basel) 2023 Aug 4;13(15).
    doi: 10.3390/ani13152514pubmed: 37570323google scholar: lookup
  2. Jonsdottir S, Stefansdottir SB, Mirkovitch J, Ziegler A, Torsteinsdottir S, Marti E. Culicoides allergens expressed in insect cells induce sulphidoleukotriene release from peripheral blood leukocytes of horses affected with insect bite hypersensitivity. Front Immunol 2025;16:1597233.
    doi: 10.3389/fimmu.2025.1597233pubmed: 40547015google scholar: lookup
  3. Graner A, Mueller RS, Geisler J, Bogenstätter D, White SJ, Jonsdottir S, Marti E. Allergen immunotherapy using recombinant Culicoides allergens improves clinical signs of equine insect bite hypersensitivity. Front Allergy 2024;5:1467245.
    doi: 10.3389/falgy.2024.1467245pubmed: 39403119google scholar: lookup
  4. White SJ, Couetil L, Richard EA, Marti E, Wilson PB. Microarray molecular mapping of horses with severe asthma. J Vet Intern Med 2024 Jan-Feb;38(1):477-484.
    doi: 10.1111/jvim.16951pubmed: 38071496google scholar: lookup
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